Intrinsic and extrinsic factors influencing the clinical course of B-cell chronic lymphocytic leukemia: prognostic markers with pathogenetic relevance

B-cell chronic lymphocytic leukemia (CLL), the most frequent leukemia in the Western world, is characterized by extremely variable clinical courses with survivals ranging from 1 to more than 15 years. The pathogenetic factors playing a key role in defining the biological features of CLL cells, hence eventually influencing the clinical aggressiveness of the disease, are here divided into "intrinsic factors", mainly genomic alterations of CLL cells, and "extrinsic factors", responsible for direct microenvironmental interactions of CLL cells; the latter group includes interactions of CLL cells occurring via the surface B cell receptor (BCR) and dependent to specific molecular features of the BCR itself and/or to the presence of the BCR-associated molecule ZAP-70, or via other non-BCR-dependent interactions, e.g. specific receptor/ligand interactions, such as CD38/CD31 or CD49d/VCAM-1. A putative final model, discussing the pathogenesis and the clinicobiological features of CLL in relationship of these factors, is also provided

Sometimes even Dr Google is wrong: An unusual contact dermatitis caused by benzoyl peroxide

The use of the internet to obtain medical information is becoming increasingly common among patients as a substitute for consulting a healthcare provider. The present case is a typical example of sequelae of self-diagnosis and self-therapy in a patient who preferred to look for a “do-it-yourself” solution online

Systemic allergic dermatitis due to gentamicin

The sensitizing potential of aminoglycosides is well known and neomycin is the most commonly reported contact allergen. We report a case of systemic allergic dermatitis related to the use of topical gentamicin

Seven years-experience of adalimumab therapy for Hidradenitis Suppurativa in a real-life dermatologic setting

Introduction Hidradenitis Suppurativa (HS) often causes severe impairment of the quality of life of patients affected, as it is characterized by recurrent relapses of inflammation and predisposes to retractive scars, with severe alteration of anatomy of the affected regions. Adalimumab is currently the only approved long-term biological therapy for this disease. Material and method We retrospectively review the data of HS patients treated with Adalimumab at the ‘Hidradenitis Suppurativa Clinic’, University of Ferrara, Italy since the drug was first available to October 2020. The aim is to describe our real-life experience in a clinical outpatient service. We assessed the main demographic features, therapy duration, reasons of suspension and efficacy (evaluated by HiSCR – Hidradenitis Score) in relation to surgical procedures, hospitalization, number of areas involved by the disease and BMI > 30. We also assessed the aspects related to the use of adalimumab’s biosimilar. Results Data on 76 patients, with a mean age of 38.26 ± 14.74 years and mean BMI 28.10 ± 5.92 were collected. Most of the treated patients had Hurley stage III (58/76); mean Sartorius score was 115.5 ± 55.86, mean IHS4 was 76.1 ± 44.3. A statistically significant correlation between hospitalization and cessation of adalimumab, the loss of the achievement of the HiSCR, and surgery was found. No need to do surgery was a protective factor against the failure of adalimumab treatment, meaning that the most severe cases are more likely to fail the biological therapy. Conclusion New scenarios are opening up in clinical practice: the arrival of biosimilars allow greater sustainability of expenditure, while the anti-IL17 allow the patient who has failed therapy with adalimumab a valid and safe therapeutic option to be undertaken. A comprehensive care including hospitalization, a specific antibiotic therapy and surgical treatment is often mandatory to achieve a satisfactory control of the disease

B-cell chronic lymphocytic leukemia

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Molecular Oncology: B-cell chronic lymphocytic leukemia

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KID Syndrome and Hidradenitis Suppurativa: A Rare Association Responding to Surgical Treatment

Background: Keratitis-ichthyosis-deafness (KID) syndrome is a rare genodermatosis characterized by keratitis, neurosensorial auditory impairment and ichthyosiform skin involvement. Frequent complications of the syndrome are chronic, opportunistic cutaneous infections, and the development of skin cancers. Several cases of association between KID syndrome and other conditions, including hidradenitis suppurativa (HS), are described in the literature. This correlation could be explained by the hyperproliferative state of the epidermis, which occurs in KID syndrome and may favor follicular plugging. Objectives: The aim of this study was to describe a very rare case of association between KID syndrome and HS and its complex therapeutic management. Results: The failure of the drugs commonly used in HS and the excellent results of surgery, although difficult to achieve, were experienced. Conclusion: Despite the technical difficulties related to surgery, namely, cutaneous superinfections, frequent dehisce of the suture, and closure by secondary intention, the authors strongly recommend the surgical approach in these patients

MDM4 (MDMX) is overexpressed in chronic lymphocytic leukaemia (CLL) and marks a subset of p53wild-type CLL with a poor cytotoxic response to Nutlin-3

In the present study, moving from the gene expression signature that identified a a subgroup of p53wt CLL showing a lack of response to the in-vitro treatment with Nutlin-3, we eventually identified MDM4 as a gene that, despite its peculiar over-expression in a subset of Nutlin-3 \u2018non-responder\u2019 p53wt CLL, turned out to be universally over-expressed by CLL cells compared to normal B cells. This observation is in keeping with studies describing the over-expression of MDM4 in primary samples from several solid tumours, including glioblastoma, retinoblastoma, breast, colon, and lung cancers, and may contribute to identify MDM4 as a potentially useful new therapeutic target also for CLL. Preclinical studies indicating the anti-neoplastic effects of MDM4 down-regulation in murine lymphoma models are of further support for this hypothesis

The IGHV1-69/IGHJ3 recombinations of unmutated CLL are distinct from those of normal B cells

IGHV1-69/51p1 is expressed by ? 30% of unmutated chronic lymphocytic leukemia (U-CLL) and combines with selected IGHD and IGHJ genes generating stereotypes if HCDR3 amino acid homology is &gt; 60%. We had previously revealed stereotypic IGHV1-69/IGHJ6 rearrangements in normal naive B cells, thereby identifying potential counterparts of U-CLL. A different stereotypic IGHV1-69/IGHD3-16(RF2)/IGHJ3 rearrangement carrying the CAR(GGx)YD motif in the N1-region, recurrent in 6% IGHV1-69+ve CLL, is exceptionally sequence restricted, strongly suggestive of shared antigen recognition. We have now analyzed IGHV1-69/IGHJ3 rearrangements in circulating B cells of healthy individuals using several PCR-based approaches with IGHV1-69/IGHJ3 CLL sequences for reference. Stereotypes were found, but all were distinct from CLL. Remarkably, even a highly sensitive semi-nested PCR, specific for the CLL-expressed IGHV1-69/IGHD3-16(RF2)/IGHJ3 stereotype, failed to identify the CAR(GGx)YD sequence, although similar motifs were found. These highly specific B cells are not apparent in the accessible normal repertoire and may expand in response to rarely expressed antigens important in the pathogenesis of CLL.<br/